Producing renewable sources for a variety of fuels and chemicals is of great importance to a world with increasing demand for such products. While petroleum is a product of decayed plant and other matter that has been incubated beneath the earth's surface for millions of years, some efforts today focus on the direct use of plants and other organisms to generate, e.g., lipids, which can include fatty acids and derivatives thereof, for use in the fuel and chemical industries. Fatty acids are composed of long alkyl chains, similar to petroleum, and are a primary metabolite used by cells for both chemical and energy storage functions. Improving the scalability, controllability, and cost-effectiveness of producing fatty acids and fatty acid derivatives (collectively “fatty acid products”) would be beneficial to the development of renewable energy and chemical sources.
Fatty acid synthesis in a cell is a repeating cycle where malonyl-acyl carrier protein (malonyl-ACP) is condensed with a carbon substrate to form a growing chain of acyl-ACP. Fatty acid production by engineered cyanobacteria has been described in U.S. Appl. Pub. No. 2009/0298143, which discloses introducing a non-native gene encoding a fatty-acyl-ACP thioesterase to release fatty acids from ACP. However, as with many cellular processes, feedback inhibition by intermediates and/or various end-products may limit production of fatty acids. For example, feedback inhibition of key fatty acid synthesis enzymes, such as ACCase, FabH, and FabI, is mediated by medium- to long-chain acyl-ACPs. See Handke et al., Metabolic Eng. 13:28-37 (2011); FIG. 1 (dashed line).